Methadone Didanosine

Drugs that may affect nelfinavir include anticonvulsants, azithromycin, azole antifungals, efavirenz, delavirdine, HMG-CoA reductase inhibitors, indinavir, interleukins, nevirapine, rifabutin, rifampin, ritonavir, saquinavir, St. John s wort. Drugs that may be affected by nelfinavir include amiodarone, antiarrhythmics (amiodarone, quinidine), azithromycin, benzodiazepines, efavirenz, ergot alkaloids, delavirdine, didanosine, fentanyl, indinavir, lamivudine methadone, nonsedating antihistamines, oral contraceptives, phenytoin, pimozide, quinidine, rifabutin, saquinavir, sildenafil, sirolimus, tacrolimus, zidovudine. 

Drugs that might affect amprenavir include abacavir, aldesleukin, antacids, anticonvulsants, azole antifungals, clarithromycin, cyclosporine, dexamethasone, buffered didanosine, disulfiram, ethanol, indinavir, methadone, metronidazole, nelfinavir, nonnucleoside reverse transcriptase inhibitors, oral contraceptives, rifamycins, ritonavir, saquinavir, St. John s wort, tacrolimus, and zidovudine. 

Drugs that may affect didanosine include allopurinol, methadone, and ganciclovir. Drugs that may be affected by didanosine include ganciclovir, antacids, antifungal agents, antiretroviral drugs, fluoroquinolones, and stavudine. 

Drugs that may interact with stavudine include didanosine, doxorubicin, hydroxyurea, methadone, ribavirin, and zidovudine. 

Drugs that may be affected by peginterferon alfa-2a include theophylline, methadone, and NRTIs (eg, didanosine, zidovudine, stavudine). 

The buffer in didanosine tablets and powder interferes with absorption of indinavir, delavirdine, atazanavir, dapsone, itraconazole, and fluoroquinolone agents therefore, administration should be separated in time. Serum levels of didanosine are increased when -administered with tenofovir or ganciclovir, and are decreased by atazanavir, delavirdine, ritonavir, tipranavir, and methadone (Table 49-4). 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Allopurinol increases didanosine plasma concentrations and their coadministration is not recommended. Ganciclovir, tenofovir and disoproxil also increase didanosine plasma concentrations, and dose reduction is recommended. Conversely, methadone decreases didanosine plasma concentrations, and appropriate doses for the combination have not been established. Didanosine should not be administered with drugs that cause pancreatic or neurotoxicity. Ribavirin increases its risk of toxicity and should not be coadministered. 

In those who are opioid-dependent, methadone can facilitate adherence to HAART regimens. The pharmacokinetics of the tablet formulations of didanosine and stavudine have been studied in 17 individuals taking stable methadone therapy in comparison with 10 untreated controls (33). Methadone reduced the AUCo 6 by 63% for didanosine and by 25% for stavudine and the C ax by 66% and 44% respectively. These effects appeared to result primarily from reduced systemic availability. Trough concentrations of methadone were comparable to those seen in historical controls, suggesting that the nucleoside analogues did not affect methadone disposition. The authors concluded that larger doses of the tablet formulation (or another type of formulation) may be necessary to provide HAART in subjects taking methadone. 

Rainey PM, Friedland G, McCance-Katz EF, Andrews L, Mitchell SM, Charles C, JatlowP. Interaction of methadone with didanosine and stavndine. J Acquit Immune Defic Syndr 2000 24(3) 24I-8. 

Noninterfering acetaminophen, amphotericin B, brotizolam, ceftazidime, ciprofloxacin, codeine, diclofenac, didanosine, domperidone, fluoxetine, foscarnet, gangiclovir, methadone, metoclopramide, mianserin, nystatin, pyrimethamine, ranitidine, sulfamethoxazole, temazepam, trimethoprim, zidovudine... 

A sampling of commonly used drugs with cytochrome P450-mediated metabolism inhibited by ketoconazole or other azoles includes chlordiazepoxide, cisapride, cyclosporine, didanosine, fluoxetine, loratadine, lovastatin, methadone, nifedipine, phenytoin, quinidine. theophylline, verapamil, warfarin, and zolpidem. 

A study in 17 subjects taking methadone found that the AUC and maximum levels of didanosine tablets were 57% and 66% lower, respectively, when compared with 10 control subjects. Trough levels of methadone did not differ from historical controls, suggesting that didanosine had no effect on methadone pharmacokinetics. A later study found that there was no reduction in the AUC of didanosine given as enteric-coated capsules. ... 

Uncertain. It appears that methadone reduces the bioavailability of dida-nosine, and to a lesser extent, stavudine, possibly because it delays gastric emptying. Thus, the enteric-coated didanosine preparation appears not to be affected. Conversely, methadone apparently reduces the glucuroni-dation of the zidovudine by the liver, resulting in an increase in its serum levels. Methadone may also reduce renal clearance of zidovudine."... 

The reduction in didanosine levels with methadone may be clinically relevant, and the authors suggest increasing the dose of the tablet formulation. Monitor virological response. The enteric-coated didanosine preparation is not affected and it may therefore be worth considering using this preparation instead. 

Friedland G, Rainey P, Jatlow P, Andrews L, Damle B, McCance-Katz E. Phannacokinetics of didanosine from encapsulated enteric coated bead formulation vs chewable tablet fonnu-lation in patients on chronic methadone dierapy. XIV International AIDS Conference, Barcelona, 2002. Abstract TuPeB4548. 

Simultaneous didanosine, folic acid, ganciclovir, lamivudine, nevirapine, pyrazinamide, ranitidine, rifampin, stavudine, sulfamethoxazole, trimethoprim, zidovudine Noninterfering adefovir, amprenavir, delavirdine, efavirenz, fluconazole, indinavir, itraconazole, methadone, nelfinavir, oxazepam, pyrimethamine, rifampin, ritonavir, saquinavir, zalcitabine... 

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